Childhood Onset Arthritis Research Articles

ROSAH syndrome: childhood-onset arthritis, hand deformities, uveitis, and splenomegaly.

ROSAH syndrome: childhood-onset arthritis, hand deformities, uveitis, and splenomegaly.

Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions.

Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features. Therefore, we set out to investigate the functional alterations of synovial monocytes in childhood-onset arthritis, how they acquire this phenotype, and whether these mechanisms could be used to tailorize treatment. The function of synovial monocytes was analysed by assays believed to reflect key pathological events, such as T-cell activation-, efferocytosis- and cytokine production assays using flow cytometry in untreated oligoarticular juvenile idiopathic arthritis (oJIA) patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry and functional assays. To characterize pathways induced by synovial fluid, we utilized broad-spectrum phosphorylation assays and flow cytometry, as well as inhibitors to block specific pathways. Additional effects on monocytes were studied through co-cultures with fibroblast-like synoviocytes or migration in transwell systems. Synovial monocytes display functional alterations with inflammatory and regulatory features, e.g., increased ability to induce T-cell activation, resistance to cytokine production following activation with LPS and increased efferocytosis. In vitro, synovial fluid from patients induced the regulatory features in healthy monocytes, such as resistance to cytokine production and increased efferocytosis. IL-6/JAK/STAT signalling was identified as the main pathway induced by synovial fluid, which also was responsible for a majority of the induced features. The magnitude of synovial IL-6 driven activation in monocytes was reflected in circulating cytokine levels, reflecting two groups of low vs. high local and systemic inflammation. Remaining features, such as an increased ability to induce T-cell activation and markers of antigen presentation, could be induced by cell-cell interactions, specifically via co-culture with fibroblast-like synoviocytes. Synovial monocytes in childhood-onset arthritis are functionally affected and contribute to chronic inflammation, e.g., via promoting adaptive immune responses. These data support a role of monocytes in the pathogenesis of oJIA and highlight a group of patients more likely to benefit from targeting the IL-6/JAK/STAT axis to restore synovial homeostasis.

P64 Accurate incidence and prevalence estimates are important for families of children with juvenile idiopathic arthritis

Introduction/BackgroundJuvenile Idiopathic Arthritis (JIA) is a heterogenous group of autoimmune disorders characterised by chronic joint inflammation, affecting children and young people (CYP) under the age of 16. Recent analysis in the UK [1] has provided an update to the estimated incidence and prevalence of JIA.Whilst the policy and health-care benefits of accurate incidence and prevalence rates are understood, this patient- and parent-led qualitative project sought views from parents of CYP with JIA to understand whether knowing accurate estimates of incidence and prevalence are important to them.Description/MethodParents of CYP with JIA, all members of a small online group on social media, were asked whether knowing accurate rates of JIA were important to them, and why. Responses were collated and summarized.Discussion/ResultsWhilst a few respondents felt it did not matter to them what the overall rates of JIA were, focusing instead on their own personal experience with the condition, the majority did want to know and gave consistent reasoning.They advised that, when your child is diagnosed with JIA, it is a very isolating experience. Most people have never heard of the condition before, and being told your child has arthritis is a frightening time (especially if you then become aware of some of the significant long-term effects, such as potential continuation of disease into adulthood and possible joint damage, and the side effects of treatment, and social impacts of the disease [2, 3]. Whilst direct support is available to families affected by JIA (www.jarproject.org/hope), understanding prevalence rates can help reduce mental health burdens on patients and parents and reduce feelings of isolation.Families also advised that they want to know numbers of children with JIA so we collectively can get a better understanding of the cause, the trends, and the possible reasons behind changes. Knowing accurately the numbers of children with JIA can help to raise awareness; current lack of awareness in society and primary care contributes to delays in diagnosis and potentially worse clinical outcomes [4]. In addition they reported the need for appropriate resourcing of paediatric rheumatology and support services, and the political and financial discussions that must take place to enable that to happen need to be supported by evidence.Key learning points/ConclusionOverall, parents do want to know how many other children have JIA. It takes some of the isolation and anxiety away to know you are not alone. It matters because knowing there are other parents in the same situation as you can help reduce anxiety and loneliness. It matters, because knowing there are researchers focussing on JIA helps remind you that work is underway to better understand JIA, its causes, and improved treatments which will eventually lead to improved care for children with the condition. It matters, because it can help target resources appropriately. It matters, because raising awareness is more effective if we know how many people are affected by a chronic condition. And it matters, because as improved treatments are developed we want to be able to see the number of children categorised as having active JIA to reduce and health outcomes for each child to improve.

Modern concepts of vitamin D role in juvenile idiopathic arthritis in children (review)

Arthritis is one of the most common chronic rheumatic diseases in children. Juvenile idiopathic arthritis (JIA) is the current nomenclature that is used to refer to a group of diseases that include chronic arthritis, childhood-onset arthritis of unknown cause. The etiology of JIA is unknown and the pathogenesis is likely to be multifactorial. One of the risk factors for the development of this disease is an insufficient level of vitamin D in the blood serum. The purpose of the analysis of the literature data was to compile and interpret data on the current point of view on the status of vitamin D in children with JIA. This article summarizes reports about the role of vitamin D in the development and clinical manifestation of juvenile arthritis (JA). Plenty of studies show a low level of vitamin D in blood serum in children with juvenile arthritis. At the same time, the role of low vitamin D status in the initiation of juvenile idiopathic arthritis development, activation of the inflammatory process, and further prognosis is controversial. The questions about vitamin D supplementation, its duration and dosage are still relevant. Five biomedical literature search bases were accessed, in the following order: Medline (using Ovid), Embase (using Ovid), Cumulative Index to Nursing and Allied Health Literature (CINHAL), Web of Science, and Scopus.

The relationship between adverse childhood experiences (ACEs) and childhood-onset arthritis

The relationship between adverse childhood experiences (ACEs) and childhood-onset arthritis

Adverse Childhood Experiences Are Associated with Childhood-Onset Arthritis in a National Sample of US Youth: An Analysis of the 2016 National Survey of Children's Health

To determine whether there is an association between adverse childhood experiences (ACEs) and childhood-onset arthritis, comparing youth with arthritis to both healthy youth and youth with other acquired chronic physical diseases (OCPD); and to examine whether ACEs are associated with disease-related characteristics among children with arthritis. In a cross-sectional analysis of data from the 2016 National Survey of Children's Health we examined whether ACEs were associated with having arthritis vs either being healthy or having a nonrheumatologic OCPD. ACE scores were categorized as 0, 1, 2-3, ≥4 ACEs. Multinomial logistic regression models examined associations between ACEs and health status while adjusting for age, sex, race/ethnicity, and poverty status. Among children with arthritis, associations between ACEs and disease-related characteristics were assessed by Pearson χ2 analyses. Compared with children with no ACEs, children with 1, 2-3, and ≥4 ACEs had an increased odds of having arthritis vs being healthy (adjusted OR for ≥4 ACEs, 9.4; 95% CI, 4.0-22.1) and vs OCPD (adjusted OR for ≥4 ACEs, 3.7; 95% CI-1.7, 8.1). Among children with arthritis, ACEs were associated with worse physical impairment. Children with higher numbers of ACEs are more likely to have arthritis, when arthritis status is compared either with being healthy or with having OCPD. Further studies are needed to determine the direction of the association between ACEs and childhood arthritis, its impact on disease course, and potential intervention targets that might mitigate these effects.

Depressive symptoms, pain and disability for adolescent patients with juvenile idiopathic arthritis: results from the Childhood Arthritis Prospective Study.

ObjectivesTo determine if depressive symptoms assessed near diagnosis associate with future measures of pain, disability and disease for adolescent patients diagnosed with JIA.MethodsData were analysed from JIA patients aged 11–16 years recruited to the Childhood Arthritis Prospective Study, a UK-based inception cohort of childhood-onset arthritis. Depressive symptoms (using the Mood and Feelings Questionnaire; MFQ), active and limited joint count, disability score (Childhood Health Assessment Questionnaire), pain visual analogue scale and patient’s general evaluation visual analogue scale were collected. Associations between baseline measures (first visit to paediatric rheumatologist) were analysed using multiple linear regression. Linear mixed-effect models for change in the clinical measures of disease over 48 months were estimated including MFQ as an explanatory variable.ResultsData from 102 patients were analysed. At baseline, median (IQR) age was 13.2 years (11.9–14.2 years) and 14.7% scored over the MFQ cut-off for major depressive disorder. At baseline, depressive symptoms significantly associated with all clinical measures of disease (P ⩽ 0.01). High baseline depressive symptoms scores predicted worse pain (P ⩽ 0.005) and disability (P ⩽ 0.001) 12 months later but not active and limited joint counts.ConclusionsAdolescent patients with JIA and depressive symptoms had more active joints, pain and disability at the time of their first specialist appointment. The associations between baseline depression and both pain and disability continued for at least one year, however, this was not the case for active joint count.

Research Review: Childhood chronic physical illness and adult emotional health - a systematic review and meta-analysis.

Childhood chronic physical illness is associated with a greater vulnerability for emotional problems (i.e. depression and anxiety) in childhood. However, little is known about life-long effects of childhood chronic physical illness on mental health. The present study aims to systematically review evidence for associations between eight chronic physical illnesses with childhood onset (arthritis, asthma, cancer, chronic renal failure, congenital heart disease, cystic fibrosis, type 1 diabetes, and epilepsy) and adult emotional problems. A database search of MEDLINE, PsycARTICLES, PsycINFO, and ScienceDirect was undertaken, and random effects meta-analyses were used to synthesise evidence from eligible studies. In total, 37 studies were eligible for the systematic review (n=45,733) and of these, 34 studies were included in the meta-analyses (n=45,358). There were overall associations between childhood chronic physical illness and adult depression (OR=1.31; 95% CI [1.12, 1.54]) and anxiety (OR=1.47; 95% CI [1.13, 1.92]). Separate meta-analyses for childhood asthma, type 1 diabetes and cancer were also conducted, with cancerbeing significantly associated with adult depression (OR=1.19; 95% CI [1.00, 1.42]). The effects of childhood chronic physical illness on the risk of emotional problems persist beyond childhood and adolescence. Mental health prevention and intervention strategies targeting children with chronic physical illnesses can have long-term benefits.

FRI0085 Social status of adult patients with childhood onset arthritis

BackgroundProblems of social rehabilitation of adult patients with childhood onset arthritis are not well studied though very urgent.ObjectivesTo assess social status of adult patients with childhood onset arthritis.MethodsAnalysis of database...

SAT0108 Arthritis with childhood onset in adult patients

BackgroundDespite active therapy in adult patients with childhood onset arthritis, the aim of therapy is not always achieved, which explains non satisfactory outcomes.ObjectivesTo analysis of database of adults with childhood...

GALACTOSYLATION OF IgG ASSOCIATED OLIGOSACCHARIDES: REDUCTION IN PATIENTS WITH ADULT AND JUVENILE ONSET RHEUMATOID ARTHRITIS AND RELATION TO DISEASE ACTIVITY

The prevalence of agalactosyl N-linked oligosaccharides on serum IgG was determined for patients with juvenile onset and with adult rheumatoid arthritis. A. significant difference in the prevalence of these structures from age matched controls was found in both types of arthritis. In patients with adult onset rheumatoid arthritis, the results showed a strong correlation between the prevalence of IgG-associated agalactosyl oligosaccharides and disease activity. A correlation between disease activity and agalactosyl structures was also seen in a retrospective analysis of serial IgG samples from patients with juvenile onset disease. The finding that childhood onset arthritis and adult rheumatoid arthritis share a defect of glycosylation of serum IgG suggests that there may be a greater similarity between these two varieties of rheumatoid arthritis than has been hitherto considered. The observation that the incidence of agalactosyl oligosaccharides on IgG fluctuates with disease activity provides indirect evidence for a seminal role for this change of glycosylation in the inflammatory process which, in rheumatoid arthritis, is focused on the synovial tissues and results in bone erosions and joint destruction.

Frequency of HLA-Dw3 in juvenile rheumatoid arthritis.

We have prospectively examined 46 consecutive unrelated children with JRA, 28 females and 18 males, for HLA‐A, ‐B, ‐Dw1, and ‐Dw3 antigens. The data were analyzed according to mode and age of onset, as well as presence of extraarticular features. Patients with JRA were found to have an elevated frequency of HLA‐B27 (26% vs. 8% of controls, P < 0.01). This elevated frequency of HLA‐B27 was noted in patients with either a pauciarticular or polyarticular onset and consistent with previous observations, was more common in males than females. However, the most striking associations in JRA were apparent when the MLC‐defined locus HLA‐Dw3 was studied. The total patient population had a 46% frequency of HLA‐Dw3 as compared with 24% in controls (P < 0.01). Moreover, when the group of 46 children was subdivided, the HLA‐Dw3 frequency of patients with polyarticular disease was 64% as compared with 21% in pauciarticular disease (P < 0.01). Further, although the frequency of HLA‐B8 was similar in JRA to that in the control panel, a significant degree of linkage disequilibrium was shown to exist between HLA‐B8 and HLA‐Dw3. No such linkage was shown to exist between HLA‐B27 and either HLA‐Dw1 or Dw3. Although we have not multiplied the P value by the number of HLA‐A, ‐B and ‐D antigens, we suggest that the presence of the MLC‐defined locus HLA‐Dw3 is significantly elevated in children with polyarticular mode of onset of JRA and suggest that further definition of lymphocyte‐dependent loci may aid in understanding the mechanism of pathogenesis as well as the classification and prognosis of childhood onset arthritis.

10 - Arthritis of Childhood Onset

SUMMARY In conclusion, immunogenetic studies in childhood onset arthritis have proven valuable in defining subtypes of ‘juvenile rheumatoid arthritis’ or ‘juvenile chronic polyarthritis’; HLA-B27 is associated with pauciarticular arthritis in older onset boys who have many hallmarks of early ankylosing spondylitis. This association of HLA-B27 with a particular subgroup of children with chronic arthritis points out the value of considering patients and their types of diseases with care so that findings of basic medical science can be accurately applied to clinical medicine. This assocation would have been lost had all children with chronic arthritis been lumped together as having the same disease. There is preliminary evidence that some HLA-D antigens and B lymphocyte specificities may be associated with certain JRA subgroups; further studies are warranted in this regard. Childhood onset ankylosing spondylitis, Reiter's disease, spondylitis of bowel disease, and reactive arthritis are associated with HLA-B27 in children as they are in adults.

The association of antinuclear antibodies with the chronic iridocyclitis of juvenile rheumatoid arthritis (Still's disease).

AbstractPositive tests for antinuclear antibodies (ANA) were found in 51 of 58 (88%) patients with chronic iridocyclitis and juvenile rheumatoid arthritis (Still's disease). Antinuclear antibodies were predominantly of the IgG class of immunoglobulins and were generally present in liters of 1:50 (six ANA units) or more. They were unassociated with disease activity, severity or duration, age of patient at onset or testing, or sex. Neither other autoantibodies nor antibodies reactive with DNA or RNA were associated. In 8 patients tested early in disease, ANA were found prior to the onset of iridocyclitis. The presence of ANA should prove useful in identifying patients with JRA at risk for chronic iridocyclitis. In contrast, negative tests for ANA in patients with childhood‐onset arthritis and iridocyclitis were found to be associated with acute iridocyclitis and subsequent ankylosing spondylitis.